As part of our continuing studies of the origin of Colorado tick fever virus within erthrocytes, we have been looking for the presence of virus within the nucleated cells of erythroid differentiation in order to evaluate our previously proposed hypothesis that viral replication within infected stem cells of the bone marrow, concurrent with red cell differentiation of the infected stem cell, results in the presence of virus within erythrocytes. The proposed studies are designed to show evidence of viral synthesis within erythropoietic cells undergoing mitosis and enucleation. To attain such a goal, the optimum time to inoculate fetuses in utero relative to the optimum period during gestation and/or relative to the optimum fetal size must be determined. Due to the minute size of fetal mouse livers, a large number of fetuses must be inoculated and the liver from each fetus surviving at least 3 days must be individually monitored for antigen concentration (by fluorescent antibody staining) in order to insure a pool containing a relatively high concentration of infected erythropoietic cells. In addition, a satisfactory method for the concentration of mitotic cells from fetal mouse livers must be determined in order to increase the probability of demonstrating by electron microscopy a mitotic cell containing Colorado tick fever virus and/or structures indicative of viral infection. BIBLIOGRAPHIC REFERENCES: Cremer, N.E. Oshiro, L.S., Weil, M.L., Lennette, E.H. Itabashi, H.H. and Carnay, L. Isolation of rubella virus from brain chronic progressive panencephalitis. J. Gen. Virol. 29: 143-154, 1975. Oshiro, L.S., Cremer, N.E., Norris, F.H. Jr., and Lennete, E.H. Virus-like particles in muscle from a patient with amyotrophic lateral sclerosis. Neurology 26: 57-60, 1976. Results of this work also presented at the spring meeting of the Northern California Branch, American Society for Microbiology, April 3, 1976, Syntex Laboratories, Inc., Palo Alto, California.